Pathological assessment of sentinel lymph-node biopsies in patients with breast cancer.
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Axilla↗
Biomedical subjects
C W Elston
Publications and source records attributed to C W Elston.
Value of contralateral surveillance mammography for primary breast cancer follow-up.
Mammographic screening of the contralateral breast is often advocated during follow-up of women previously treated for primary operable breast cancer. The purpose of this study was to determine the value of this investigation. Between 1987 and 1995 a total of 5102 contralateral screening mammograms were performed biennially on 2511 women aged </= 70 years following treatment for primary operable breast cancer. Sixty-five metachronous contralateral breast cancers were identified: 21 (32%) at routine clinical examination, 24 (37%) at mammography, and 20 (31%) by patients between routine follow-up appointments. The prognostic features of metachronous cancers were better or similar to those of the first cancer in 59 of 65 (91%) cases. Because of the favorable prognostic characteristics of the contralateral cancer, mammographic screening may have contributed to the long-term survival of 16 of 26 women in whom the histologic characteristics of the first cancer predicted a good prognosis. The cancer detection rate with mammography for these women was 6.5 per 1000 contralateral mammogram investigations at a cost of pound3852 per cancer detected. The results of this study suggest that surveillance mammography of the contralateral breast is of value in women whose first cancer predicted a favorable prognosis.
Adult↗
Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.
It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.
Breast↗
Metaplastic carcinoma of the breast arising within complex sclerosing lesion: a report of five cases.
AIMS: This study presents a series of five cases in which metaplastic carcinoma, predominantly low-grade adenosquamous carcinoma, of the breast is seen arising within a background of a complex sclerosing lesion. This association has been recognized previously but has not been documented in detail. This study describes the characteristics of the components present in each case and discusses the existing literature. This observation adds further evidence to support an association between some types of invasive breast carcinoma and sclerosing lesions of the breast. METHODS AND RESULTS: Four of these cases were received as referral cases for opinion. The fifth was received as part of the routine surgical workload within our own institution. Two patients presented following mammographic screening and three symptomatically; their mean age was 62 years (range 49-68). The mean lesion size was 16 mm (range 7-24). All five lesions showed features of a complex sclerosing lesion/radial scar in the form of central sclerosis with elastosis and radiating benign entrapped tubules. One had associated benign papillary structures and two had focal benign squamous metaplasia. Four cases showed coexisting but distinct areas of low-grade adenosquamous carcinoma with glandular and squamous epithelial differentiation in a spindle cell background. One case had associated undifferentiated spindle cell carcinoma. Detailed immunophenotypic characteristics of two cases are presented. CONCLUSIONS: This series illustrates a postulated but previously unconfirmed association between an unusual form of metaplastic breast carcinoma (adenosquamous carcinoma) and complex sclerosing lesions. The mechanisms of induction of breast carcinoma are poorly understood but these observations further emphasize the potential for sclerosing lesion of the breast to be associated with, and possibly give rise to, invasive carcinoma of different types. The precise nature of the interaction between the pathological processes remains unclear.
Aged↗
An immunohistochemical examination of the expression of E-cadherin, alpha- and beta/gamma-catenins, and alpha2- and beta1-integrins in invasive breast cancer.
This study examines the expression of the cell-cell adhesion molecules E-cadherin and its associated proteins, the catenins and the matrix-cell adhesion molecules beta1- and alpha2-integrins, in primary invasive breast carcinoma. Expression was assessed immunohistochemically on frozen sections by semi-quantitative scoring of the intensity and proportion of immunoreactivity in 55 cases. Associations with each other and with other histological and prognostic features and survival were sought. There was a significant association between loss of E-cadherin expression and loss of alpha- and beta/gamma-catenin immunostaining. In 20 per cent of cases, membranous immunoreactivity with E-cadherin antibody was absent. Absent cytoplasmic expression of alpha- and beta/gamma-catenins was seen in 24 and 22 per cent of breast cancers, respectively. The intensity of reactivity with E-cadherin showed a significant association with histological grade (p=0.002) and tumour type (p<0.001). Lobular carcinomas frequently showed loss of expression of E-cadherin, as reported elsewhere; loss of catenin expression was also found in these tumours. alpha-catenin intensity also showed a relationship with grade (p=0.008) and with oestrogen receptor (ER) status (p=0.006). beta/gamma-catenin expression was not associated with other known prognostic factors. Forty-nine per cent and 42 per cent of cases showed no membrane immunostaining with beta1- and alpha2-integrin, respectively, and co-ordinated loss of beta1- and alpha2-integrin expression was found. Both beta1- and alpha2-integrin expression were associated with histological grade (p=0.003 and p=0.031, respectively) and beta1 immunoreactivity with tumour type (p=0.010). None of the variables examined showed a statistically significant association with tumour size or lymph node stage, or with overall survival, although a trend was seen (p=0.087) towards poorer survival of patients with tumours with absent or weak expression of beta1-integrin. The expression of these markers is of biological interest, but appears to be of little additional use in predicting clinical behaviour.
Adult↗
Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.
A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.
Breast Diseases↗
The prognosis of small primary breast cancers.
The Nottingham Prognostic Index (NPI) is an integrated prognostic index used to predict patient survival for women with invasive breast cancer. The index is based on invasive tumour size, histological lymph node stage and tumour grade. The value of such an index has been questioned in small invasive breast cancers and it has been suggested that size is the only necessary prognostic determinant. The aims of this study were to determine the extent of regional lymph node involvement and survival in women with small invasive breast cancers and to assess the value of the NPI. Between 1976 and 1994, 2684 women aged < or = 70 years were treated for primary operable invasive breast cancers of < or = 5 cm in maximum diameter, of which 318 measured < or = 1 cm. Follow-up data were evaluated to determine histological factors important in predicting survival outcomes in women with cancers < or = 1 cm in diameter and comparing their survival according to the NPI with all women treated for primary operable breast cancers < or = 5 cm in maximum diameter. Histological lymph node involvement was demonstrated in 56/318 (18%) of cancers of < or = 1 cm in diameter. Significant survival differences were demonstrated for small breast cancers according to lymph node stage, vascular invasion and histological tumour grade. Only lymph node stage and histological tumour grade were independent prognostic indicators using a multivariate Cox model. The survival curves for small tumours stratified by the NPI were similar to those of cancers up to 5 cm in diameter. The results indicate that lymph node staging and histological grading are still important prognostic determinants for breast cancers < or = 1 cm in diameter. An axillary node staging procedure should be performed for all invasive breast cancers < or = 1 cm in diameter. The NPI remains relevant for small breast cancers.
Adult↗
Pathological prognostic factors in breast cancer.
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Breast Neoplasms↗
Microinvasive carcinoma of the breast: diagnostic criteria and clinical relevance.
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Breast Neoplasms↗
Clinical and histological predictors of contralateral breast cancer.
AIMS: Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast. The purpose of this study was to assess the annual incidence of metachronous contralateral breast cancer (CBC) and to identify factors that predict for its development. METHODS: A retrospective study was performed on 3211 women aged </=70 years treated for primary operable breast cancer between 1975 and 1995. RESULTS: Eighty-three developed CBC prior to locoregional or distant recurrence from the first primary. The clinical incidence of CBC was 6.4 per 1000 women years, three to four times the risk of occurrence of breast cancer in the general female population (or a risk of six to eight times to the remaining breast). Strong family history, age of onset <50 years and lobular histology were significant factors predicting for CBC in univariate and multivariate models. Other clinical factors (previous hormone therapy, chemotherapy, radiotherapy) or histological factors (DCIS, invasive tumour size, grade, vascular invasion, lymph node and oestrogen receptor status) were not significant predictors for CBC. CONCLUSIONS: In women previously treated for primary operable breast cancer, early age of onset and a strong family history are predictors for the subsequent development of metachronous CBC. Ipsilateral mastectomy with contralateral prophylactic mastectomy with or without immediate breast reconstruction is a reasonable option for a young woman diagnosed with breast cancer and who has a strong family history, particularly if the cancer has histological features suggesting a good prognosis.
Aged↗
A critical appraisal of existing classification systems of epithelial hyperplasia and in situ neoplasia of the breast with proposals for future methods of categorization: where are we going?
Current classification systems for borderline lesions of the breast including epithelial hyperplasia, atypical hyperplasia, and ductal carcinoma in situ fall short of the ideal. They present pathologists with problems of recognition or clear distinction and clinicians with difficult management choices. In addition, recent evidence indicates that different pathogenetic lesions are present in some categories. This article presents a brief critical appraisal of the existing classifications and offers suggestions for revision using a model of pathogenetic lineage.
Breast↗
The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy.
BACKGROUND: Histologic grade is well recognized for its prognostic significance in cases of primary operable invasive breast carcinoma; however, the majority of studies in which grade has been assessed have been based on single-center trials. In addition, the role of grade in predicting response to chemotherapy has not been examined in many previous studies. METHODS: The authors assessed the value of Nottingham histologic grade (NHG) in a group of 465 patients enrolled in a multicenter, randomized International Breast Cancer Study Group clinical trial of adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative primary breast carcinoma (formerly named Ludwig Trial V). RESULTS: NHG was a predictor of overall survival for both LN negative and LN positive patients (P=0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis for both LN positive and LN negative patients, with hazard ratios of 1.651 (P < 0.001) and 1.437 (P=0.045), respectively, for an increase of one grade. Among LN negative patients, this survival disadvantage was observed only for those who received perioperative chemotherapy. For LN positive patients, an increase of one grade resulted in a significant overall survival disadvantage regardless of whether prolonged or perioperative chemotherapy was given. For LN negative patients grouped by grade, there was no observed difference in overall or disease free survival according to whether perioperative chemotherapy or no adjuvant therapy was given. However, LN positive patients with Grade 3 tumors had a significantly greater overall and disease free survival benefit from prolonged chemotherapy than from perioperative chemotherapy (P=0.016 and P=0.013, respectively); LN positive patients with Grade 1 or 2 disease in both treatment arms had comparable overall and disease free survival. A strong correlation between the previously utilized Bloom-Richardson grading system (BRG) and NHG was observed (P < 0.001 and kappa=82%) and no apparent differences in overall and disease free survival were observed between the two systems. NHG did, however, identify a greater proportion of tumors as Grade 1, and BRG identified a greater proportion of breast carcinomas as Grade 3. CONCLUSIONS: This multicenter clinical study confirms the value of histologic grade, and the authors propose that this technique be used to identify Grade 3, LN positive patients who will benefit from prolonged rather than perioperative chemotherapy.
Antimetabolites, Antineoplastic↗
The accuracy of breast ultrasound in the evaluation of clinically benign discrete, symptomatic breast lumps.
INTRODUCTION: Recent reports have suggested that breast ultrasound (US) is of value in distinguishing malignant from benign processes. The aim of this study was to establish the accuracy of US in detecting invasive malignancy in clinically benign, discrete, symptomatic breast lumps. METHODS: The US appearances of 205 clinically benign breast masses were documented prospectively and prior to mammography by one radiologist (AJE). The US appearances were then correlated with the fine needle aspiration (FNA), core biopsy and surgical findings and compared with the mammographic findings. RESULTS: The US findings were normal 72 (35%), simple cyst 63 (31%), solid benign 51 (25%), solid indeterminate 15 (7%) and solid malignant four (2%). Ultrasound characterized 13 (93%) of the 14 patients found to have invasive carcinoma as indeterminate or malignant. No patients with normal or simple cyst US findings had invasive malignancy. Ultrasound had significantly better accuracy (97% vs 87%, P < 0.02) sensitivity (93% vs 57%, P < 0.05) and negative predictive value (99% vs 92%, P < 0.002) than mammography in the detection of invasive carcinoma when indeterminate and malignant imaging findings were taken as positive. CONCLUSION: US is a useful adjunct to FNA/core biopsy in confirming the nature of symptomatic, clinically benign breast masses and is superior to mammography in this clinical setting.
Adult↗
Prognostic factors in invasive carcinoma of the breast.
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Biomarkers↗
Screening women aged less than 50 years with a family history of breast cancer.
Family history is an important breast cancer risk factor and is a common reason for referral to specialist breast clinics for consideration of breast screening. The aims of this study were to determine cancer detection rates and prognostic features of breast cancers identified in women aged less than 50 years at increased risk of breast cancer who attend a Family History Breast Screening Clinic (FHC). Between January 1988 and December 1995, 1371 asymptomatic women aged less than 50 years underwent annual clinical breast examination and biennial mammography due to a family history of breast cancer. A total of 29 cancers (23 invasive and 6 in situ) were detected or presented as interval cancer during a mean follow-up of 22 months (range 0-96 months). This gave a relative risk for invasive breast cancer in this high-risk group of 5 when compared with an age-matched female population in the U.K. The cancer screening detection rates were similar to those of women aged 50 years or over undergoing population screening in the NHS Breast Screening Programme (NHSBSP)--FHC prevalent screen 8 per 1000 screening visits versus NHSBSP 6.5 per 1000, FHC incident screen 3.3 per 1000 screening visits versus NHSBSP 3.8 per 1000. A higher proportion of in situ cancers were detected in the FHC screened group compared with cancers identified in symptomatic patients from an age-matched risk group (21% versus 4%). No differences were demonstrated for invasive tumour size, grade or lymph node stage between symptomatic and screened women. The early results of this study suggests that young women at risk of breast cancer due to a family history may benefit from regular breast screening due to the early detection of in situ lesions.
Adolescent↗
A simple index to predict prognosis independent of axillary node information in breast cancer: comment.
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Axilla↗
Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology.
The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening, the greater use of breast-conserving surgery, and the recognition that certain histological subtypes are associated with a greater risk of local recurrence has led to the formulation of several new classifications of DCIS in recent years. There are, however, no data concerning the degree of consistency with which these schemes can be applied by reasonable numbers of pathologists. Thirty-three cases of DCIS were thus examined by a working group of 23 European pathologists who categorized them using five recently published classifications: (1) that of the European Pathologists' Working Group based on differentiation (a combination of nuclear grade and cell polarization) with categories of poorly, intermediately, and well differentiated; (2) one based entirely on nuclear grade with categories of high, intermediate, and low, currently in use in the UK national and EC-funded breast screening programs; (3) the same classification in which only two categories, high nuclear grade and other, were used; (4) the Van Nuys system in which lesions are divided into high grade, non-high grade with necrosis and non-high grade without necrosis; and (5) a two-category classification based entirely on the presence or absence of comedo necrosis. Of the three systems with three categories, Van Nuys gave the highest overall kappa statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that assessing cell polarization in addition to nuclear grade neither improves nor worsens consistency. In all three systems, the middle category was associated with the lowest value for kappa. Of the two systems with two categories, that based on nuclear grade gave the highest overall kappa of 0.46 and that based on comedo necrosis the lowest of 0.34. The most robust histological features were thus high- and low-grade nuclei and necrosis as long as the latter did not involve the recognition of a comedo growth pattern. These values probably represent the maximum achievable, at least by reasonable numbers of pathologists in everyday practice. They are better than those previously reported for classification based entirely on architecture, but further improvement is needed.
Breast Neoplasms↗
Radiological features of papillary carcinoma of the breast.
Seventeen patients with papillary carcinoma of the breast were analysed with respect to the radiological findings by three experienced breast radiologists. The most frequent mammographic appearance of papillary tumours was of an ill-defined (70%) and lobulated (60%) mass and at ultrasound as a well-defined (76%), inhomogeneous (62%) and hypoechoic (92%) lesion. Histopathological subtypes of encysted papillary carcinoma, encysted papillary carcinoma with an invasive focus and invasive papillary carcinomas could not be predicted from the radiological features, although invasive tumours tended to be larger at presentation than the other subtypes.
Breast Neoplasms↗